The effects of both the long acting thyroid stimulator (LATS) and pituitary thyrotropin (TSH) appear to be mediated by cyclic adenosine monophosphate (cAMP). We have developed an in vivo assay system for TSH and LATS in which changes in mouse thyroid cAMP (TcAMP) are measured as an index of stimulation. We have shown that age and diet iodine effect the TSH and LATS induced changes in mouse TcAMP and that there is variation among other species in the TcAMP response to TSH. No change of thyroid cyclic guanosine monophosphate content was observed after administration of TSH or LATS. We propose to investigate control of TcAMP by defining the effects of animal age and diet iodine, as well as species, on TSH and LATS induced changes in TcAMP. We shall also evaluate changes in TcAMP in animals of both sexes. We plan to determine if cyclic inosine monophosphate (cIMP) and uridine monophosphate (cUMP) are present in the thyroid and if so, whether they respond to TSH and LATS. We shall examine the serum and thyroid tissue of patients with hyperthyroidism for factors other than LATS that increase TcAMP, by testing serum and tissue for LATS activity; neutralizing the LATS if present; and then retesting the serum or tissue in order to isolate other TcAMP stimulators. We propose to visualize the sites of localication of cAMP in normal and abnormal thyroid tissue by immunofluorescent techniques and relate the localization of cAMP to its concentration in normal and abnormal human thyroid tissue.